Fred Winston
Fred Marshall Winston, Ph.D.
John Emory Andrus Professor of Genetics

A critical step in eukaryotic gene regulation is the control of transcription across the chromatin template. While transcription has been extensively studied for many years, there are still many mysteries regarding its function and regulation. Furthermore, in humans, when transcription is aberrant, it can often lead to different diseases, including cancer. Transcription was once thought to occur primarily over open reading frames to produce mRNAs. However, it is now known to be pervasive, also occurring on antisense strands and in intergenic regions. While some of this transcription has been shown to play regulatory roles, the function of most transcription is poorly understood.

Our lab studies eukaryotic transcription and chromatin structure using yeast as a model system. Yeast is an excellent model system, as there is extensive conservation between yeast and humans. In addition, by studying yeast one can use powerful genetic approaches that are not possible in larger eukaryotes. For example, high-resolution genetic screens and selections can be performed to study any aspect of gene regulation. In addition, any desired DNA sequence changes can be made in the yeast genome and its consequences analyzed, allowing rigorous in vivo analysis. Furthermore, the small yeast genome facilitates many types of genome-wide, deep-sequencing approaches, including those used to measure mRNA levels (RNA-seq), nucleosome positions (MNase-seq), and the binding of transcription factors (ChIP-seq). The small genome size of yeast, coupled with the ability to make genomic changes, also allows the study and elucidation of complex traits. Finally, as unicellular eukaryotes, yeast cells are valuable for the biochemical analysis of protein complexes and post-translational modifications.

Spt6 regulates intragenic and antisense transcription, nucleosome positioning, and histone modifications genome-wide in fission yeast.
Authors: Authors: DeGennaro CM, Alver BH, Marguerat S, Stepanova E, Davis CP, Bähler J, Park PJ, Winston F.
Mol Cell Biol
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The S. pombe SAGA complex controls the switch from proliferation to sexual differentiation through the opposing roles of its subunits Gcn5 and Spt8.
Authors: Authors: Helmlinger D, Marguerat S, Villén J, Gygi SP, Bähler J, Winston F.
Genes Dev
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Evidence that Spt10 and Spt21 of Saccharomyces cerevisiae play distinct roles in vivo and functionally interact with MCB-binding factor, SCB-binding factor and Snf1.
Authors: Authors: Hess D, Winston F.
Genetics
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Histone H3 lysine 4 methylation is mediated by Set1 and required for cell growth and rDNA silencing in Saccharomyces cerevisiae.
Authors: Authors: Briggs SD, Bryk M, Strahl BD, Cheung WL, Davie JK, Dent SY, Winston F, Allis CD.
Genes Dev
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Functional organization of the yeast SAGA complex: distinct components involved in structural integrity, nucleosome acetylation, and TATA-binding protein interaction.
Authors: Authors: Sterner DE, Grant PA, Roberts SM, Duggan LJ, Belotserkovskaya R, Pacella LA, Winston F, Workman JL, Berger SL.
Mol Cell Biol
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TBP mutants defective in activated transcription in vivo.
Authors: Authors: Arndt KM, Ricupero-Hovasse S, Winston F.
EMBO J
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Biochemical and genetic characterization of a yeast TFIID mutant that alters transcription in vivo and DNA binding in vitro.
Authors: Authors: Arndt KM, Ricupero SL, Eisenmann DM, Winston F.
Mol Cell Biol
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Isolation and analysis of a novel class of suppressor of Ty insertion mutations in Saccharomyces cerevisiae.
Authors: Authors: Fassler JS, Winston F.
Genetics
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Conserved regulators of nucleolar size revealed by global phenotypic analyses.
Authors: Authors: Neumüller RA, Gross T, Samsonova AA, Vinayagam A, Buckner M, Founk K, Hu Y, Sharifpoor S, Rosebrock AP, Andrews B, Winston F, Perrimon N.
Sci Signal
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Chromatin- and transcription-related factors repress transcription from within coding regions throughout the Saccharomyces cerevisiae genome.
Authors: Authors: Cheung V, Chua G, Batada NN, Landry CR, Michnick SW, Hughes TR, Winston F.
PLoS Biol
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